title: Monocyte responses in the context of Q fever: from a static polarized model to a kinetic model of activation.
abstract: BACKGROUND
  Q fever is caused by Coxiella burnetii, a bacterium that persists in M2-polarized macrophages. We wondered whether the concept of M1/M2 polarization is applicable to Q fever patients.
  
  
  METHODS
  Monocytes from healthy controls were cultured with IFN-γ and IL-4, agonists of M1 and M2 macrophages, respectively, and their gene expression was assessed using whole-genome microarrays. Selected biomarkers were assessed in blood from Q fever patients by real-time reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Monocytes exhibited early (6-hour) patterns of activation specific to IFN-γ or IL-4 and a late (18-hour) pattern of common activation. Because these responses were not reducible to M1/M2 polarization, we selected biomarkers and tested their relevance in Q fever patients. The early genes NLRC5, RTP4, and RHOH, which were modulated in response to IFN-γ, were up-regulated in patients with acute Q fever, and the expression levels of the late genes ALOX15, CLECSF1, CCL13, and CCL23 were specifically increased in patients with Q fever endocarditis. The RHOH and ALOX15 genes were associated with the activity of acute Q fever and Q fever endocarditis, respectively.
  
  
  CONCLUSIONS
  Our results show that the kinetic model of monocyte activation enables a dynamic approach for the evaluation of Q fever patients.
authors.affiliation: Aix-Marseille University, URMITE, CNRS UMR 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016997:Coxiella burnetii; D004697:Endocarditis, Bacterial / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D046228:Microarray Analysis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011778:Q Fever / Q000276:immunology*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Q fever; macrophage; microarray; monocyte; polarization